In Reply: Starting insulin therapy (original) (raw)
Diabetes & Metabolism, 2006
There are many reasons to believe that in the near future, the treatment of patients with Type 2 diabetes will be characterised by an increased use of insulin therapy. To ensure that insulin regimens are acceptable to patients, and implemented by physicians, they should be as simple and efficient as possible. Simplicity is synonymous with the regimen of once-daily basal insulin glargine given at any time of the day (at the same time each day). With such a strategy, the dose is adjusted by titrating to target fasting blood glucose values of 5.0-7.2 mmol/L (90-130 mg/dL). When these targets can no longer be achieved with reasonable doses of long-acting insulin, a rapid-acting insulin analogue should be added at meal times. A step-by-step strategy can be used; it is recommended that initially, a single daily prandial bolus of a rapid-acting insulin analogue is administered before the meal that leads to the highest post-meal blood glucose excursions. Further boluses can be added at other meal times as necessary, i.e, when postmeal blood glucose values remain above 10.0 mmol/L (180 mg/dL) and 7.8 mmol/L (140 mg/dL) at mid-morning and 2h-post-lunch or post-dinner times, respectively. This stepwise strategy may eventually lead to a standard basal-bolus regimen with 3 pre-meal injections of rapid-acting insulin analogues, a potentially small trade-off for achieving fairly-well controlled diabetes.
Diabetes, obesity & metabolism, 2018
To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily basal insulin glargine. This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG < 130 mg/dL were randomized (1:1) to either arm A (no sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage. A total of 121 patients were randomized to arm A (n = 61) o...
Benefits of timely basal insulin control in patients with type 2 diabetes
Journal of Diabetes and its Complications, 2015
Worldwide, both underdiagnosis and undertreatment leave many patients exposed to long periods of hyperglycemia and contribute to irreversible diabetes complications. Early glucose control reduces the risk of both macrovascular and microvascular complications, while tight control late in diabetes has little or no macrovascular benefit. Insulin therapy offers the most potent antihyperglycemic effect of all diabetes agents, and has a unique ability to induce diabetes remission when used to normalize glycemia in newly diagnosed patients. When used as a second-line therapy, basal insulin is more likely to safely and durably maintain A1C levels ≤7% than when insulin treatment is delayed. The use of basal insulin analogs is associated with a reduced risk of hypoglycemia and weight gain compared to NPH insulin and pre-mixed insulin. Patient selftitration algorithms can improve glucose control while decreasing the burden on office staff. Finally, recent data suggest that addition of incretin agents to basal insulin may improve glycemic control with very little, if any increased risk of hypoglycemia or weight gain.
Diabetes, Obesity and Metabolism, 2003
Background: The glycaemic control of thrice daily treatment with premixed biphasic insulin aspart (BIAsp) without other antidiabetic therapy was tested in type 2 diabetic patients, in order to compare the glucose control of a 'high' mixture (BIAsp 70) or a 'medium' mixture (BIAsp 50) (70 or 50% soluble IAsp and 30 or 50% protamine-crystallized IAsp, respectively) administered just before dinner. Aim: To compare these regimens to conventional 30 : 70 premixture on a twice a day basis. Methods: This randomized, double-blind, two-period crossover study included 16 patients with type 2 diabetes. Twenty four-hour serum glucose and insulin profiles were obtained thrice: (1) after a one-week run-in period with biphasic human insulin (BHI) 30/70 twice daily (run-in), (2) after 4 weeks of treatment with thrice daily BIAsp 70 before breakfast, lunch and dinner (Dinner70 regimen) and (3) after 4 weeks of BIAsp 70 before breakfast and lunch and BIAsp 50 before dinner (Dinner50). Results: Daytime average serum glucose was lower with Dinner70 compared to run-in (9.6 AE 0.39 mmol/l vs. 11.2 AE 0.61 mmol/l, p < 0.05). Postprandial glucose excursions after breakfast and lunch were lower, but fasting morning glucose was higher during the treatment periods than in the run-in period. Twenty four-hour C-peptide AUC was considerably lower during both treatment periods than in the run-in period (run-in/Dinner50 ratio 1.29 [1.08; 1.54] p < 0.01; run-in/Dinner70 ratio 1.31 [1.08;1.58], p < 0.01). Conclusions: Switching the dinner dose to BIAsp 50 did not alter overall glucose control significantly from that provided with BIAsp 70. Exploratory analyses between the two active treatment regimens and run-in/BHI indicate that thrice daily BIAsp 70 administration: (1) for optimization of the night-time control, the dinner dose needs adjustment or replacement by a premixed insulin with a larger proportion of basal insulin than BIAsp 50 and (2) none of the premixtures adequately provide for both the evening meal and overnight requirements.
Journal of Diabetes and its Complications, 2012
Problem: Frequent dosage adjustments are necessary to achieve effective insulin therapy. However, a controversy surrounds the pertinent clinical parameters required to make effective and safe insulin titrations. We hypothesize that glucose readings are sufficient to adjust insulin dosage provided that it is done on a weekly basis. Methods: In a prospective pilot study, we recruited 14 subjects with suboptimally controlled insulin-treated Type-2 and Type-1 diabetes. Subjects were treated with basal-bolus insulin therapy that was titrated weekly for 12 weeks. Dosage adjustments were made by the study Endocrinologist by reviewing subjects' glucose readings, exclusively based on logsheets and contingent upon the approval of the on-site study team. To corroborate that the glucose readings were sufficient for making dosage adjustments, we used software to process only glucose readings and recommend insulin dosage adjustments. The recommendations made by the software were retrospectively compared to the ones made by the study Endocrinologist. Results: All N = 568 recommendations were approved by the study team and in 99.3% of the cases the recommendations were clinically similar to the ones made by the software. No hazardous disagreements were found. The mean A1C improved from 9.8% (±2.0) to 7.9% (±1.3) (p = 0.001) in 12 weeks and the weekly mean glucose progressively improved from 220.3 mg/dl (±51.9) to 151.5 mg/dl (±19.2) (p b 0.0001). The frequency of minor hypoglycemia was 22.7 per patient-year in subjects with Type-2 diabetes and 42.7 in the subjects with Type-1 diabetes. No severe hypoglycemic events occurred. Conclusions: Glucose readings are sufficient to adjust insulin therapy in a safe and effective manner, when adjustments are made on a weekly basis. Thus, dedicated software may help adjust insulin dosage between clinic visits. Published by Elsevier Inc. ☆ Author Disclosure Statement: Both Israel Hodish and Eran Bashan are affiliated with Hygieia INC. a company developing medical devices based on the described software. The PI and the study team in New-Jersey are not affiliates of Hygieia and did not participate in the preparation of the manuscript.
Diabetes Care, 2014
We compared two strategies initiating and intensifying insulin treatment and tested for noninferiority of premixed insulin to basal 6 mealtime insulin analog in patients eating light breakfasts. This randomized, open-label, 48-week study compared two algorithms. Up to three injections of insulin lispro mix 25 and/or insulin lispro mix 50 (premix; premixed insulin lispro) or basal insulin glargine plus up to three injections of insulin lispro (basal+; glargine + insulin lispro) were used in type 2 diabetic patients uncontrolled with oral antihyperglycemic medication and consuming <15% daily calories at breakfast. The hypothesis was to test noninferiority of premix to basal+ for glycemic control measured by HbA 1c after 48 weeks, assessed using ANCOVA with a 0.4% margin. Patients (n = 344; 176 [51%] females; mean [SD] age 54.3 [8.8] years; BMI 29.4 [4.6] kg/m 2 ; baseline HbA 1c 9.02 [0.97]%) were randomized to premix (n = 171) or basal+ (n = 173). In the per-protocol analysis (n = 230), least squares means (95% CI) end point HbA 1c were 7.40% (7.15-7.65) and 7.55% (7.27-7.82) in respective arms. Between-treatment difference was 20.14% (20.42 to 0.13), with noninferiority met. Significantly more patients in premix achieved HbA 1c targets of <7.0% compared with basal+ (48.2 vs. 36.2%; P = 0.024). Self-monitored blood glucose profiles, body weight changes, total insulin doses, and overall hypoglycemia (65 vs. 60%) were similar in premix and basal+ (P = 0.494), except nocturnal episodes (34.3 vs. 23.7%; P = 0.018) were more common in premix. Both intensive insulin strategies improved glycemic control; however, final HbA 1c levels were seen above those achieved in previous treat-to-target trials, likely due to the inadequate insulin titrations and probably due to the complexity of tested insulin regimens. A higher percentage of patients achieved target HbA 1c <7% with multiple premixed insulins, but this treatment resulted in more nocturnal hypoglycemia than a basal-bolus regimen.